This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims of this research study are: a) to identify a link between memory loss in Mild Cognitive Impairment (MCI) and mild Alzheimer's Disease (AD) and mutations in the Hfe gene, b) examine affective, cognitive and memory components of MCI and AD and their relationship to Hfe gene mutations, c) investigate neurological correlates in brain iron content using MRI imaging (T2, T2* and R*) and participants'cognitive and memory functioning and their Hfe gene mutation status and d) investigate the olfactory deficits reported in early AD using an olfactory fMRI paradigm. The objective of this longitudinal research study is to examine whether participants identified as MCI will progress more rapidly to AD if they carry the Hfe mutation and show significant oxidative stress and elevated brain-iron levels (assessed via high-resolution MRI scans). A considerable amount of effort and funding has gone into identifying genetic risk factors in neurodegenerative diseases in general, and Alzheimer's Disease (AD) in particular. A recent set of studies has reported that the Hfe mutation is not only associated with an increased risk of AD, but also earlier onset. This research proposal is significant because it offers the potential for development of therapeutic intervention. The Hfe gene is associated with iron overload disorders. Thus, the significance of our studies is that contributions of Hfe gene mutations to AD may be preventable by interventions such as dietary manipulation, phlebotomy or chelation therapy.